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1.
Artigo em Inglês | MEDLINE | ID: mdl-39384082

RESUMO

BACKGROUND: Despite numerous reported benefits of robotic mitral repair, the absolute number of procedures performed remain low in part to uncertainties about the necessary steps to launch a program. In this report, we describe our early outcomes and strategy with launching a successful new robotic mitral repair program. METHODS: Our multimodal strategic plan emphasized team education, hands-on technical preparation, stepwise advancement, and careful patient selection. Consultant service analytics and team debriefings allowed for iterative improvements. RESULTS: Between March 2022 and February 2024, 50 patients underwent robotic mitral repair at our institution. Average age at time of operation was 62 years with a Society of Thoracic Surgeons risk score of 0.58. Successful repairs were performed in 98% of patients. There was 1 conversion to sternotomy. There were no deaths, and there was minimal perioperative morbidity. On both predischarge and follow-up echocardiography, no patients had greater than mild mitral regurgitation. CONCLUSIONS: Our work provides a model for establishing a successful robotic mitral program. An up-front emphasis on team education, careful preparation, proper patient selection, and feedback-driven improvements can accelerate the attainment of standards set by high-volume centers.

2.
Int J Artif Organs ; 47(6): 401-410, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38853663

RESUMO

INTRODUCTION: A feared complication of an acute myocardial infarction (AMI) is cardiac arrest (CA). Even if return of spontaneous circulation is achieved, cardiogenic shock (CS) is common. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) supports patients with CS and is often used in conjunction with an Impella device (2.5 and CP) to off-load the left ventricle, although limited evidence supports this approach. METHODS: The goal of this study was to determine whether a mortality difference was observed in VA-ECMO alone versus VA-ECMO with Impella (ECPELLA) in patients with CS from AMI and CA. A retrospective chart review of 50 patients with AMI-CS and CA and were supported with VA-ECMO (n = 34) or ECPELLA (n = 16) was performed. The primary outcome was all-cause mortality at 6-months from VA-ECMO or Impella implantation. Secondary outcomes included in-hospital mortality and complication rates between both cohorts and intensive care unit data. RESULTS: Baseline characteristics were similar, except patients with ST-elevation myocardial infarction were more likely to be in the VA-ECMO group (p = 0.044). The ECPELLA cohort had significantly worse survival after VA-ECMO (SAVE) score (p = 0.032). Six-month all-cause mortality was not significantly different between the cohorts, even when adjusting for SAVE score. Secondary outcomes were notable for an increased rate of minor complications without an increased rate of major complications in the ECPELLA group. CONCLUSIONS: Randomized trials are needed to determine if a mortality difference exists between VA-ECMO and ECPELLA platforms in patients with AMI complicated by CA and CS.


Assuntos
Oxigenação por Membrana Extracorpórea , Parada Cardíaca , Coração Auxiliar , Mortalidade Hospitalar , Infarto do Miocárdio , Choque Cardiogênico , Humanos , Oxigenação por Membrana Extracorpórea/efeitos adversos , Oxigenação por Membrana Extracorpórea/métodos , Oxigenação por Membrana Extracorpórea/mortalidade , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , Parada Cardíaca/terapia , Parada Cardíaca/mortalidade , Parada Cardíaca/fisiopatologia , Infarto do Miocárdio/complicações , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/terapia , Idoso , Choque Cardiogênico/terapia , Choque Cardiogênico/mortalidade , Choque Cardiogênico/fisiopatologia , Resultado do Tratamento , Função Ventricular Esquerda
3.
BMC Med Educ ; 24(1): 587, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38807106

RESUMO

PURPOSE: Physician-scientists play a crucial role in advancing biomedical sciences. Proportionally fewer physicians are actively engaged in scientific pursuits, attributed to attrition in the training and retention pipeline. This national study evaluated the ongoing and longer-term impact of the COVID-19 pandemic on stress levels, research productivity, and optimism for physician-scientists at all levels of training. METHODS: A multi-institutional cross-sectional survey of medical students, graduate students, and residents/fellows/junior faculty (RFJF) was conducted from April to August 2021 to assess the impact of COVID-19 on individual stress, productivity, and optimism. Multivariate regression analyses were performed to identify associated variables and unsupervised variable clustering techniques were employed to identify highly correlated responses. RESULTS: A total 677 respondents completed the survey, representing different stages of physician-scientist training. Respondents report high levels of stress (medical students: 85%, graduate students: 63%, RFJF: 85%) attributed to impaired productivity concerns, concern about health of family and friends, impact on personal health and impairment in training or career development. Many cited impaired productivity (medical students: 65% graduate students: 79%, RFJF: 78%) associated with pandemic impacts on training, labs closures and loss of facility/resource access, and social isolation. Optimism levels were low (medical students: 37%, graduate students: 38% and RFJF: 39%) with females less likely to be optimistic and more likely to report concerns of long-term effects of COVID-19. Optimism about the future was correlated with not worrying about the long-term effects of COVID-19. Since the COVID-19 pandemic, all respondents reported increased prioritization of time with family/friends (67%) and personal health (62%) over career (25%) and research (24%). CONCLUSIONS: This national survey highlights the significant and protracted impact of the COVID-19 pandemic on stress levels, productivity, and optimism among physician-scientists and trainees. These findings underscore the urgent need for tailored support, including mental health, academic, and career development assistance for this biomedical workforce.


Assuntos
Pesquisa Biomédica , COVID-19 , Estudantes de Medicina , Humanos , COVID-19/epidemiologia , Estudos Transversais , Feminino , Masculino , Estudantes de Medicina/psicologia , Adulto , Pandemias , Docentes de Medicina/psicologia , Inquéritos e Questionários , Estresse Psicológico/epidemiologia , Pesquisadores/psicologia , Pesquisadores/educação , SARS-CoV-2 , Otimismo , Médicos/psicologia
4.
JACC Case Rep ; 29(10): 102322, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38601846

RESUMO

Uhl anomaly is characterized by the morphologic absence of right ventricular myocardium and is an exceedingly rare cause of nonischemic cardiomyopathy. We report the first case of a successful heart transplantation in a 41-year-old patient who presented in cardiogenic shock from Uhl anomaly causing decompensated right ventricular failure.

5.
ASAIO J ; 70(9): 758-766, 2024 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-38446842

RESUMO

Mechanical circulatory support (MCS) as a bridge to lung transplant is an infrequent but accepted pathway in patients who have refractory end-stage pulmonary failure. The American Association of Thoracic Surgeons Expert Consensus Guidelines, published in 2023, recommends venovenous (VV) extracorporeal membrane oxygenation (ECMO) as the initial configuration for those patients who have failed conventional medical therapy, including mechanical ventilation, while waiting for lung transplantation and needing MCS. Alternatively, venoarterial (VA) ECMO can be used in patients with acute right ventricular failure, hemodynamic instability, or refractory respiratory failure. With the advancement in percutaneous venopulmonary (VP) ECMO cannulation techniques, this option is becoming an attractive configuration as bridge to lung transplantation. This configuration enhances stability of the right ventricle, prevents recirculation with direct introduction of pulmonary artery oxygenation, and promotes hemodynamic stability during mobility, rehabilitation, and sedation-weaning trials before lung transplantation. Here, we present a case series of eight percutaneous VP ECMO as bridge to lung transplant with all patients mobilized, awake, and successfully transplanted with survival to hospital discharge.


Assuntos
Oxigenação por Membrana Extracorpórea , Transplante de Pulmão , Humanos , Oxigenação por Membrana Extracorpórea/métodos , Transplante de Pulmão/métodos , Masculino , Feminino , Adulto , Insuficiência Respiratória/terapia , Insuficiência Respiratória/cirurgia , Insuficiência Respiratória/etiologia , Pessoa de Meia-Idade
6.
Ann Thorac Surg ; 117(4): 804-811, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37527699

RESUMO

BACKGROUND: We sought to evaluate whether the anatomic and physiologic stratification system (ACAP score), released as part of the American College of Cardiology/American Heart Association updated guidelines for management of adult congenital heart disease (ACHD) in 2018, better estimated mortality and morbidity after cardiac operations for ACHD. METHODS: The ACAP score was determined for 318 patients (age ≥18 years) with ACHD undergoing heart surgery at our institution between December 2001 and August 2019. The primary end point was perioperative mortality. The secondary aim was to evaluate the performance of the ACAP, The Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery (STAT) Congenital Heart Surgery Mortality Categories, and ACHS mortality scores/categories at predicting a composite adverse outcome of perioperative mortality, prolonged ventilation, and renal failure requiring replacement therapy. Logistic regression models were built to estimate mortality and the composite outcome using anatomic and physiologic components independently and together. Receiver operating characteristic curves were created, and area under the curves were compared using the Delong test. RESULTS: The median age was 37 years (interquartile range, 26.3-50.0 years). There were 9 perioperative mortalities (2.8%). With respect to perioperative mortality, the area under the curve using the anatomic component only was 0.74, which improved to 0.81 after including physiologic severity (P = .05). When physiologic severity was added to the model for the composite outcome, the discriminatory abilities of the ACHS mortality score and the STAT categories increased significantly to 0.83 (95% CI, 0.75-0.91; P = .02) and 0.82 (95% CI, 0.73-0.90; P = .04), comparable to the predictive power of ACAP. CONCLUSIONS: Physiologic severity augments ability to predict mortality and morbidity after cardiac surgery for ACHD. There is need for more robust ACHD-specific risk models.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Cardiopatias Congênitas , Humanos , Adulto , Adolescente , Mortalidade Hospitalar , Estudos Retrospectivos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Morbidade , Medição de Risco
7.
Res Sq ; 2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37986886

RESUMO

Purpose: Physician-scientists play a crucial role in advancing biomedical sciences. Proportionally fewer physicians are actively engaged in scientific pursuits, attributed to attrition in the training and retention pipeline. This national study evaluated the ongoing and longer-term impact of the COVID-19 pandemic on research productivity for physician-scientists at all levels of training. Methods: A survey of medical students, graduate students, and residents/fellows/junior faculty (RFJF) was conducted from April to August 2021 to assess the impact of COVID-19 on individual stress, productivity, and optimism. Multivariate regression analyses were performed to identify associated variables and unsupervised variable clustering techniques were employed to identify highly correlated responses. Results: A total 677 respondents completed the survey, representing different stages of physician-scientist training. Respondents report high levels of stress (medical students: 85%, graduate students: 63%, RFJF: 85%) attributed to impaired productivity concerns, concern about health of family and friends, impact on personal health and impairment in training or career development. Many cited impaired productivity (medical students: 65% graduate students: 79%, RFJF: 78%) associated with pandemic impacts on training, labs closures and loss of facility/resource access, and social isolation. Optimism levels were low (medical students: 37%, graduate students: 38% and RFJF: 39%) with females less likely to be optimistic and more likely to report concerns of long-term effects of COVID-19. Optimism about the future was correlated with not worrying about the long-term effects of COVID-19. Since the COVID-19 pandemic, all respondents reported increased prioritization of time with family/friends (67%) and personal health (62%) over career (25%) and research (24%). Conclusions: This national survey highlights the significant and protracted impact of the COVID-19 pandemic on stress levels, productivity, and optimism among physician-scientists and trainees. These findings underscore the urgent need for tailored support, including mental health, academic, and career development assistance for this biomedical workforce.

10.
Artigo em Inglês | MEDLINE | ID: mdl-37064329

RESUMO

Lung cancer screening with low-dose computed tomography (LDCT) is an effective approach for the early detection of lung cancer and the reduction of lung cancer specific mortality in high risk individuals. Despite recommendations for LDCT screening by the National Comprehensive Cancer Network (NCCN) and the United States Preventive Services Task Force, the utilization of LDCT screening in clinical practice has been low. Moreover, significant disparities in the use of LDCT have been described in underserved populations, including African American or black patients, rural patients with limited access to LDCT screening facilities, and other vulnerable patient groups with known risk factors for developing lung cancer. Several patient, provider, and healthcare systems level approaches have been proposed to mitigate lung cancer screening disparities. Such approaches include raising awareness of LDCT screening benefits and the evidence in support of LDCT screening among healthcare providers, educating patients on LDCT screening and optimizing shared decision-making approaches between patients and providers, and expanding patient access to LDCT screening through free and mobile lung cancer screening programs. As lung cancer screening utilization continues to expand in clinical practice, it will be critical to continue investigating the trends, causes, and outcomes of LDCT screening disparities in underserved populations.

11.
Artigo em Inglês | MEDLINE | ID: mdl-36567048

RESUMO

Valve-sparing repair (VSR) of tetralogy of Fallot (TOF) tends to result in higher residual right ventricular outflow tract (RVOT) gradients. We evaluated the progression and clinical implications of RVOT gradients following VSR of TOF. Demographic, clinical, and operative data were retrospectively collected from consecutive TOF patients who underwent VSR at our institution between 01/2010 and 06/2021. RVOT gradient, pulmonary valve annulus (PVA) diameter and Boston Z-scores were recorded from serial echocardiograms. Data are presented as median and interquartile range or number and percentage. A total of 156 children (boys 92, 59%) underwent VSR at 6.5 (4.9-8.4) months of age and 6.6 kg (5.6- 7.7) weight. There was 1 (0.6%) operative mortality. The remaining 155 patients were followed for 69.4 months (4-106.2). RVOT gradient was 2.4m/s (1.7-2.9) at discharge. It transiently increased, then declined and stabilized during follow-up. PVA Z-score was -1.7 (-3.1 to 0.5) at discharge and 'grew' to -0.8 (-1.7 to 0.4) at last follow-up. Freedom from RVOT re-intervention was 97%, 94% and 91% at 1, 5 and 10-year follow-up. Among 67 (43%) patients with PVA Z-score < -2, a similar RVOT gradient pattern was observed and freedom from RVOT re-intervention was 97%, 95% and 95% at 1, 5 and 8-year follow-up. Following VSR of TOF, RVOT gradients transiently increase and then fall as PVA growth catches up, resulting in durable intermediate outcomes. Patients with PVA Z-score < -2 demonstrated a similar pattern of hemodynamics in the RVOT and excellent freedom from reintervention.

13.
Artigo em Inglês | MEDLINE | ID: mdl-36272526

RESUMO

Adjuvant chemotherapy is underutilized in clinical practice, in part, because its anticipated survival benefit is limited. We evaluated the impact of AC on overall and recurrence-free survival among completely resected pN1 NSCLC patients enrolled in the North American Intergroup phase III (JBR10) trial. A post-hoc subgroup analysis of pN1 NSCLC patients was performed. Participants were randomized to cisplatin+vinorelbine (AC) (n = 118) or observation (n = 116) following complete resection. The primary endpoint was overall survival (OS). The secondary endpoint was recurrence free survival (RFS). Kaplan-Meier methods were used to compare OS and RFS between the two treatment groups. Cox regression was used to identify factors associated with OS and RFS endpoints. Both groups had similar baseline characteristics. AC patients had improved 5-year OS (AC 61.4% vs observation 41.0%, log-rank p = .008) and 5-year RFS (AC 56.2% vs observation 39.9%, log-rank p = .011) rates compared to observation. Cox regression analyses confirmed the OS (HR 0.583, 95% CI 0.402-0.846, p = .005) and RFS (HR 0.573, 95% CI 0.395-0.830, p = .003) benefit associated with AC. AC was associated with a lower risk (HR 0.648, 95% CI 0.435-0.965, p = .0326) and a lower cumulative incidence (Subdistribution Hazard Ratio [SHR], 0.67, 95% CI 0.449-0.999, p = .0498) of lung cancer deaths. In the JBR10 trial, treatment with AC conferred a significant OS and RFS advantage over observation for pN1 NSCLC patients. These data suggest that pN1 NSCLC patients may experience a disproportionately greater clinical benefit from AC than the 6% survival advantage estimated by the LACE meta-analysis.

14.
J Cell Mol Med ; 26(20): 5181-5194, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36082581

RESUMO

Mesodermal progenitors in the second heart field (SHF) express Delta-like-ligand 4 (Dll4) that regulates Notch-mediated proliferation. As cells of SHF lineage mature to assume endocardial and myocardial cell fates, we have shown that Dll4 expression is lost, and the subsequent expression of another Notch ligand Jagged1 regulates Notch-mediated maturation events in the developing heart. A subset of SHF progenitors also matures to form the pharyngeal arch artery (PAA) endothelium. Dll4 was originally identified as an arterial endothelial-specific Notch ligand that plays an important role in blood vessel maturation, but its role in aortic arch maturation has not been studied to date secondary to the early lethality observed in Dll4 knockout mice. We show that, unlike in SHF-derived endocardium and myocardium, Dll4 expression persists in SHF-derived arterial endothelial cells. Using SHF-specific conditional deletion of Dll4, we demonstrate that as SHF cells transition from their progenitor state to an endothelial fate, Dll4-mediated Notch signalling switches from providing proliferative to maturation cues. Dll4 expression maintains arterial identity in the PAAs and plays a critical role in the maturation and re-organization of the 4th pharyngeal arch artery, in particular. Haploinsufficiency of Dll4 in SHF leads to highly penetrant aortic arch artery abnormalities, similar to those observed in the clinic, primarily resulting from aberrant reorganization of bilateral 4th pharyngeal arch arteries. Hence, we show that cells of SHF lineage that assume an arterial endothelial fate continue to express Dll4 and the resulting Dll4-mediated Notch signalling transitions from an early proliferative to a later maturation role during aortic arch development.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Proteínas de Ligação ao Cálcio , Células Endoteliais , Receptores Notch , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Artérias/metabolismo , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Ligantes , Camundongos , Camundongos Knockout , Receptores Notch/genética , Receptores Notch/metabolismo
15.
Acad Med ; 97(10): 1536-1545, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35921163

RESUMO

PURPOSE: Physician-scientists have long been considered an endangered species, and their extended training pathway is vulnerable to disruptions. This study investigated the effects of COVID-19-related challenges on the personal lives, career activities, stress levels, and research productivity of physician-scientist trainees and faculty. METHOD: The authors surveyed medical students (MS), graduate students (GS), residents/fellows (R/F), and faculty (F) using a tool distributed to 120 U.S. institutions with MD-PhD programs in April-June 2020. Chi-square and Fisher's exact tests were used to compare differences between groups. Machine learning was employed to select variables for multivariate logistic regression analyses aimed at identifying factors associated with stress and impaired productivity. RESULTS: The analyses included 1,929 respondents (MS: n = 679, 35%; GS: n = 676, 35%; R/F: n = 274, 14%; F: n = 300, 16%). All cohorts reported high levels of social isolation, stress from effects of the pandemic, and negative impacts on productivity. R/F and F respondents were more likely than MS and GS respondents to report financial difficulties due to COVID-19. R/F and F respondents with a dual degree expressed more impaired productivity compared with those without a dual degree. Multivariate regression analyses identified impacted research/scholarly activities, financial difficulties, and social isolation as predictors of stress and impaired productivity for both MS and GS cohorts. For both R/F and F cohorts, impacted personal life and research productivity were associated with stress, while dual-degree status, impacted research/scholarly activities, and impacted personal life were predictors of impaired productivity. More female than male respondents reported increased demands at home. CONCLUSIONS: This national survey of physician-scientist trainees and faculty found a high incidence of stress and impaired productivity related to the COVID-19 pandemic. Understanding the challenges faced and their consequences may improve efforts to support the physician-scientist workforce in the postpandemic period.


Assuntos
Pesquisa Biomédica , COVID-19 , Médicos , Estudantes de Medicina , Pesquisa Biomédica/educação , COVID-19/epidemiologia , Docentes , Feminino , Humanos , Masculino , Pandemias , Estados Unidos/epidemiologia
16.
J Appl Lab Med ; 7(5): 1169-1174, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35665808

RESUMO

BACKGROUND: The objective of this analysis was to compare the performance sensitivity and specificity of manufacturer-recommended signal-to-cutoff (S/Co) thresholds with modified S/Co values to estimate the prevalence of SARS-CoV-2-specific antibodies in a cohort of firefighters with a known infection history. METHODS: Plasma venipuncture samples were used for serologic analysis of firefighters in Los Angeles, CA, USA, in October 2020. Seropositivity was assessed using the manufacturer's recommended S/Co (≥1.4 IgG) and modified S/Co thresholds based on measured antibody levels in 178 negative control patients who had blood drawn prior to the emergence of COVID-19. Optimal S/Co threshold was determined by receiver operating characteristic (ROC) curve analysis. RESULTS: Of 585 firefighters included in the study, 52 (8.9%) reported having a PCR-positive test history prior to antibody testing. Thirty-five (67.3%) firefighters with a previous PCR-positive test were seropositive based on the manufacturer S/Co thresholds, consistent with an estimated 67.3% sensitivity and 100% specificity. After evaluating multiple modified S/Co thresholds based on pre-pandemic negative samples, a modified S/Co of 0.36 was found to yield optimal sensitivity (88.5%) and specificity (99.4%) by ROC curve analysis. This modified threshold improved serostatus classification accuracy by 21.2%. CONCLUSIONS: S/Co thresholds based on known negative samples significantly increase seropositivity and more accurately estimate cumulative incidence of disease compared to manufacturer-based thresholds.


Assuntos
COVID-19 , Bombeiros , Anticorpos Antivirais , COVID-19/diagnóstico , COVID-19/epidemiologia , Humanos , Incidência , Los Angeles/epidemiologia , SARS-CoV-2
17.
Am Surg ; 88(10): 2445-2450, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35575161

RESUMO

Although postoperative diet modification, exercise, and regular dietitian and surgeon follow-up are often recommended after bariatric surgery (BS), their impact on weight loss is unclear. A Retrospective chart review was conducted for patients who received sleeve gastrectomy or Roux-en-Y gastric bypass (RYGB) between August 2000 and November 2017 with telephone follow-up. Multivariable logistic regression models were used for analyses. There were 514 patients included in our study. Most were female (76.3%), mean age was 46.9 years (Standard Deviation [SD] = 11.8), and mean weight loss was 11.6 (SD = 6.5) BMI points at a mean follow-up of 7 years (SD = 4.3). Current surgeon follow-up OR = 2.08 (P < .01) was positively associated with postoperative weight loss, while current dietitian follow-up=OR .41 (P < .01) was negatively associated. Current weight loss supplement use OR = .45 (P = .03) was associated with reduced willingness to undergo surgery again. Increasing preoperative BMI OR = 1.06 (P = .04) and increasing age OR = 1.04 (P = .02) were associated with improved quality of life (QoL) due to BS. Lack of surgeon follow-up and regular dietician consultation was associated with suboptimal weight loss after BS. Older age was positively associated with improved QoL, while current weight loss supplement use was associated with lower likelihood of undergoing surgery again, both independent of weight loss.


Assuntos
Cirurgia Bariátrica , Derivação Gástrica , Nutricionistas , Obesidade Mórbida , Cirurgiões , Feminino , Seguimentos , Gastrectomia , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/cirurgia , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento , Redução de Peso
18.
Am J Med Genet A ; 188(7): 2082-2095, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35385219

RESUMO

Our previous work demonstrating enrichment of outflow tract (OFT) congenital heart disease (CHD) in children with cleft lip and/or palate (CL/P) suggests derangements in common underlying developmental pathways. The current pilot study examines the underlying genetics of concomitant nonsyndromic CL/P and OFT CHD phenotype. Of 575 patients who underwent CL/P surgery at Children's Hospital Los Angeles, seven with OFT CHD, negative chromosomal microarray analysis, and no recognizable syndromic association were recruited with their parents (as available). Whole genome sequencing of blood samples paired with whole-blood-based RNA sequencing for probands was performed. A pathogenic or potentially pathogenic variant was identified in 6/7 (85.7%) probands. A total of seven candidate genes were mutated (CHD7, SMARCA4, MED12, APOB, RNF213, SETX, and JAG1). Gene ontology analysis of variants predicted involvement in binding (100%), regulation of transcription (42.9%), and helicase activity (42.9%). Four patients (57.1%) expressed gene variants (CHD7, SMARCA4, MED12, and RNF213) previously involved in the Wnt signaling pathway. Our pilot analysis of a small cohort of patients with combined CL/P and OFT CHD phenotype suggests a potentially significant prevalence of deleterious mutations. In our cohort, an overrepresentation of mutations in molecules associated with Wnt-signaling was found. These variants may represent an expanded phenotypic heterogeneity within known monogenic disease genes or provide novel evidence of shared developmental pathways. The mechanistic implications of these mutations and subsequent developmental derangements resulting in the CL/P and OFT CHD phenotype require further analysis in a larger cohort of patients.


Assuntos
Fenda Labial , Fissura Palatina , Cardiopatias Congênitas , Adenosina Trifosfatases/genética , Fenda Labial/genética , Fissura Palatina/complicações , Fissura Palatina/epidemiologia , Fissura Palatina/genética , DNA Helicases/genética , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/epidemiologia , Cardiopatias Congênitas/genética , Humanos , Enzimas Multifuncionais/genética , Mutação , Proteínas Nucleares/genética , Projetos Piloto , Prevalência , RNA Helicases/genética , Fatores de Transcrição/genética , Ubiquitina-Proteína Ligases
19.
Surg Endosc ; 36(10): 7561-7568, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35338403

RESUMO

BACKGROUND: Gastric electrical stimulation (GES) and laparoscopic gastrectomy (LG) are known therapeutic options for medically refractory gastroparesis (MRG) although there are limited data comparing their outcomes. We aim to compare clinical outcomes between patients undergoing GES vs upfront LG for the treatment of MRG while examining factors associated with GES failure and conversion to LG. METHODS: We retrospectively analyzed 181 consecutive patients who underwent GES or LG for MRG at our institution from January 2003 to December 2017. Data collection consisted of chart review and follow-up telephone survey. Statistical analysis utilized Chi-squared, ANOVA, and multivariable logistic regression. RESULTS: Overall, 130 (72%) patients underwent GES and 51 (28%) LG as primary intervention. GES patients were more likely to have diabetic gastroparesis (GES 67% vs LG 39%, p < 0.001), while primary LG patients were more likely to have post-surgical gastroparesis (GES 5% vs LG 43%, p < 0.001). Postoperatively, primary LG patients had higher rates of major in-hospital morbidity events (GES 5% vs LG 18%, p = 0.017) and longer hospital stays (GES 3 vs LG 9 days, p < 0.001). However, over a mean 35-month follow-up period, there were no differences in the rates of major morbidity, readmissions, or mortality. Multivariable regression analysis revealed patients undergoing GES as a primary intervention were less likely to report improvement in symptoms on follow-up compared to primary LG patients OR 0.160 (95% CI 0.048-0.532). Additionally, patients who converted to LG from GES were more likely to have post-surgical gastroparesis as the primary etiology. CONCLUSION: GES as a first-line surgical treatment of MRG was associated with worse outcomes compared to LG. Post-surgical etiology was associated with an increased likelihood of GES failure, and in such patients, upfront gastrectomy may be a superior alternative to GES. Further studies are needed to determine patient selection for operative treatment of MRG.


Assuntos
Terapia por Estimulação Elétrica , Gastroparesia , Gastrectomia/efeitos adversos , Gastroparesia/etiologia , Gastroparesia/cirurgia , Humanos , Estudos Retrospectivos , Resultado do Tratamento
20.
Occup Environ Med ; 79(5): 315-318, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35074885

RESUMO

OBJECTIVE: We estimate the seroprevalence of SARS-CoV-2 antibodies among a sample of firefighters in the Los Angeles (LA), California fire department in October 2020 and compare demographic and contextual factors for seropositivity. METHODS: We conducted a serological survey of firefighters in LA, California, USA, in October 2020. Individuals were classified as seropositive for SARS-CoV-2 if they tested positive for IgG, IgM or both. We compared demographic and contextual factors for seropositivity. RESULTS: All firefighters in LA, California, USA were invited to participate in our study, but only roughly 21% participated. Of 713 participants with valid serological data, 8.8% tested positive for SARS-CoV-2 antibodies, and among the 686 with complete survey data 8.9% tested positive for antibodies. Seropositivity was not associated with gender, age or race/ethnicity. Seropositivity was highest among firefighters who reported working in the vicinity of LA International Airport, which had a known outbreak in July 2020. CONCLUSIONS: Seroprevalence among firefighters in our sample was 8.8%, however, we lack a full workplace seroprevalence estimate to compare the relative magnitude against general population seroprevalence (15%). Workplace safety protocols, such as access to personal protective equipment and testing, can mitigate increased risk of infection at work, and may have eliminated differences in disease burden by geography and race/ethnicity in our sample.


Assuntos
COVID-19 , Bombeiros , Anticorpos Antivirais , COVID-19/epidemiologia , Humanos , Los Angeles/epidemiologia , SARS-CoV-2 , Estudos Soroepidemiológicos
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